Much of the increased incidence of breast cancer can be attributed to the detection of early stage disease through increased use of mammography. Recent data based on multi-institutional clinical trials has suggested that screening of asymptomatic women in the 40-49 year age bracket may not be efficacious although studies continue to emerge that both support and contradict these findings which adds further controversy to the debate over appropriate uses of mammography. As a result, there is a critical need to investigate breast cancer detection methods that could serve either a complementary or competitive role with respect to conventional x-ray mammography. Near infrared optical interrogation of breast tissue is particularly intriguing in this regard. Unfortunately, initial experience with simple transillumination techniques did not improve present problems in conventional x-ray film mammography (e.g.lack of contrast, especially in glandular breast tissue characteristic of young women), however, recent developments in optical spectroscopy and imaging suggest that previous attempts may have prematurely discredited the overall potential of noninvasive optical imaging of breast tissue. Based on these recent developments, the applicants proposed a research plan which would provide a synthesis of existing and novel ideas concerning optical imaging of breast tissue both at the conceptual and practical levels. The principal hypothesis is that frequency domain modulation methods coupled with model-based image formation from tomographically-measured optical data provides a strong basis for an imaging methodology with clinical relevance to the detection and diagnosis of breast cancer. Specific aims include: (1) continued development of finite element image reconstruction methods; (2) the design, construction and testing of a laboratory-scale frequency domain optical imaging system using amplitude modulated light and tomographic-like excitation and data collection; (3) the evaluation and optimization of the integrated functioning of these hardware and software components using simulation and phantom experiments; and (4) the design, construction and testing of a prototype clinical imaging system and its evaluation based on preliminary data obtained during a human subjects trial. The applicants indicated that this research will contribute to the growing knowledge-base on (1) the optical characteristics of normal and malignant breast tissue, (2) the ability to perform model-based image reconstruction using laboratory and clinically measured optical data, (3) the conceptual and practical strengths and limitations of frequency domain optical approaches to breast cancer detection and diagnosis and (4) future directions for improved methodologies given successful completion of the specific aims.